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Murine Bone (murine + bone)
Terms modified by Murine Bone Selected AbstractsEffects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005I. Machida Summary Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. ,2 -agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in ,2 -agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting ,2 -agonists do not modify DCs-induced allergic airway inflammation. [source] Evasion of macrophage scavenger receptor A-mediated recognition by pathogenic streptococciEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Thomas Areschoug Abstract PRR recognize conserved structures on pathogenic microbes and are important for the defense against invading microorganisms. However, accumulating evidence indicates that many pathogens have evolved mechanisms to avoid recognition by PRR. One type of PRR is the macrophage scavenger receptor A (SR-A), which has been shown to play an important role in recognition and non-opsonic phagocytosis of pathogenic bacteria. The bacterial ligands for SR-A have been suggested to be LPS or lipoteichoic acid. Here, we use murine bone marrow-derived macrophages to analyze the role of SR-A in non-opsonic phagocytosis of two major Gram-positive pathogens, Streptococcus agalactiae (group B streptococcus; GBS) and Streptococcus pyogenes. We show that the polysaccharide capsule of GBS and the surface M protein of S. pyogenes, two important virulence factors, prevent SR-A-mediated non-opsonic phagocytosis of streptococci. The sialic acid moiety of the GBS capsule was crucial for its ability to prevent recognition by SR-A. Moreover, we show that a ligand on GBS recognized by SR-A in the absence of capsule is the surface lipoprotein Blr. These findings represent the first example of a microbial strategy to prevent recognition by SR-A and suggest that bacterial surface proteins may be of importance as ligands for SR-A. [source] Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Mariela Segura Abstract To determine whether helminth-derived products modulate dendritic cell (DC) function, we investigated the effects of excretory-secretory products (ES) and adult worm homogenate (AWH) derived from the gastrointestinal nematode Heligmosomoides polygyrus (Hp) on murine bone marrow-derived DC (BMDC). Compared to the TLR9 ligand CpG, Hp-derived products alone failed to induce DC activation. ES, but not AWH, inhibited BMDC cytokine and chemokine production and co-stimulatory molecule expression (CD40, CD86 and MHC class,II) induced by TLR ligation. TLR ligand-independent, PMA-induced DC activation was unaffected by ES. Recipients of ES-treated BMDC pulsed with OVA had suppressed Ab responses in vivo, irrespective of the Th1 or Th2 isotype affiliation, compared to recipients of control OVA-pulsed BMDC. Importantly, suppression occurred even in the presence of the potent type,1 adjuvant CpG. In contrast to untreated OVA-pulsed BMDC, ES-treated BMDC pulsed with OVA had reduced co-stimulatory molecule and cytokine expression. CD4+CD25+Foxp3, T cells, which secreted high IL-10 levels, were generated in co-cultures of OT-II OVA-specific TCR-transgenic CD4+ T cells and ES-treated BMDC. These IL-10-secreting T cells suppressed effector CD4+ T cell proliferation and IFN-, production, the latter effect mediated by an IL-10-dependent mechanism. Together, these results demonstrate that nematode ES impaired DC function and suppressed both Th1 and Th2 adaptive immune responses possibly by inducing regulatory T cells. [source] Identification of novel genes regulated by ,-melanocyte-stimulating hormone in murine bone marrow-derived dendritic cellsEXPERIMENTAL DERMATOLOGY, Issue 9 2004T. Brzoska Many strains of evidence indicate that ,-melanocyte-stimulating hormone (,-MSH) elicits its immunomodulatory activity via binding to melanocortin receptors (MC-Rs) expressed on monocytes and dendritic cells. In order to identify novel target genes regulated by ,-MSH in these cells, we prepared bone marrow-derived dendritic cell precursors from BALB/c mice and treated them with GM-CSF and IL-4 for 6 days. The MC-R profile on these immature dendritic cells was first determined by quantitative RT-PCR. Both transcripts for MC-1R and MC-5R were detected in these cells. Cells were subsequently stimulated with dinitrobenzene sulfonic acid (DNBS), ,-MSH or both substances for 2 or 16 h. After RNA preparation, cDNA synthesis and in vitro transcripton hybridization of biotinylated cRNA samples was performed on MG U74A Affymetrix gene chips. Data evaluation, cleansing, extraction and analysis of the more than 12 000 cloned genes and expressed sequence tags were performed using the GENE DATA ANALYST vs. 1 Expressionist software. Filter criteria included a minimum threshold of 100, normalization by the logarithmic mean and a quality setting of P < 0.04. Changes with a change factor of >2 were regarded as significant. As expected, stimulation with DNBS resulted in induction or upregulation of genes encoding proinflammatory cytokines, growth factors, signal transduction intermediates and transcription factors. Treatment with ,-MSH blocked the DNBS-driven upregulation of several known genes such as IL-1 or CD86. On the other hand, ,-MSH modulated the expression of several novel genes implicated in immunomodulation, e.g. IL-1, converting enzyme, IFN-, receptor, FK506-binding proteins or several neuropeptides and their receptors. These data indicate novel molecular targets by which ,-MSH exerts its immunomodulatory activities in immunocompetent cells. [source] In vitro Leishmanicidal activity of naturally occurring chalconesPHYTOTHERAPY RESEARCH, Issue 2 2001Oliver Kayser Abstract A variety of chalcones have been shown to exhibit activity against Leishmania parasites. In contrast to synthetic or semisynthetic chalcones, only a few plant-derived compounds have been investigated. To provide a scientific rational for the antiprotozoal potency of plants used in ethnomedicine and containing chalcones, and in the search for new antiprotozoal drugs, we have carried out a primary screening for in vitro leishmanicidal activity of 20 chalcones isolated from plants. The compounds were tested against extracellular promastigotes of Leishmania donovani, L. infantum, L. enrietii and L. major, and against intracellular amastigote L. donovani residing within murine macrophages. Against the extracellular Leishmania (L. donovani), most compounds were active with EC50 values between 0.07 and 2.01,µg/mL. Some of these chalcones, 2,,4,-dihydroxy-4-methoxychalcone, 2,-hydroxy-3,4-dimethoxychalcone and 2-hydroxy-4,4,-dimethoxychalcone also significantly inhibited the intracellular survival of L. donovani parasites with EC50 values between 0.39 and 0.41,µg/mL. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, all compounds with antileishmanial activities also proved to be cytotoxic to varying extents (EC50 0.19,2.06,µg/mL). Correlations between molecular structures and antileishmanial activity are discussed in detail. Specific compounds are illustrated with emphasis on their mode of action and potential for the development of selective antiprotozoal agents. Copyright © 2001 John Wiley & Sons, Ltd. [source] Toll-like receptor 2 agonist Pam3CSK4 enhances the induction of antigen-specific tolerance via the sublingual routeCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2008V. Lombardi Summary Background Sublingual immunotherapy (SLIT) has been established in humans as a safe and efficacious treatment for type I respiratory allergies. Objective In this study, we compared three Toll-like receptor (TLR) 2 ligands (Pam3CSK4, Porphyromonas gingivalis lipopolysaccharide and lipoteichoic acid) as potential adjuvants for sublingual allergy vaccines. Methods These molecules were tested in co-cultures of adjuvant-pre-treated dendritic cells (DCs) with murine naïve CD4+ T lymphocytes. Patterns of cytokine production, phenotype, proliferation and gene expression were analysed by ELISA, cytofluorometry and quantitative PCR, respectively. TLR2 ligands were subsequently tested in a model of SLIT in BALB/c mice sensitized with ovalbumin (OVA). Results Among the three TLR2 ligands tested, the synthetic lipopeptide Pam3CSK4 is the most potent inducer of IL-12p35 and IL-10 gene expression in murine bone marrow-derived DCs, as well as in purified oral myeloid DCs. Only Pam3CSK4-treated DCs induce IFN-, and IL-10 secretion by naïve CD4+ T cells. Sublingual administration of Pam3CSK4 together with the antigen in BALB/c mice sensitized to OVA decreases airway hyperresponsiveness as well as OVA-specific T-helper type 2 (Th2) responses in cervical lymph nodes dramatically. Conclusion Pam3CSK4 induces Th1/regulatory T cell responses, and as such, is a valid candidate adjuvant for sublingual allergy vaccines. [source] Effects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005I. Machida Summary Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. ,2 -agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in ,2 -agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting ,2 -agonists do not modify DCs-induced allergic airway inflammation. [source] |